IL-22–producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17–producing TH17 T cells
Open accessAbstract
Background Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases. An upregulated TH17/IL-23 pathway was demonstrated in psoriasis. Although potential involvement of TH17 T cells in AD was suggested during acute disease, the role of these cells in chronic AD remains unclear.Objective To examine differences in IL-23/TH17 signal between these diseases and establish relative frequencies of T-cell subsets in AD.Methods Skin biopsies and peripheral blood were collected from patients with chronic AD (n = 12) and psoriasis (n = 13). Relative frequencies of CD4+ and CD8+ T-cell subsets within these 2 compartments were examined by intracellular cytokine staining and flow cytometry.Results In peripheral blood, no significant difference was found in percentages of different T-cell subsets between these diseases. In contrast, psoriatic skin had significantly increased frequencies of TH1 and TH17 T cells compared with AD, whereas TH2 T cells were significantly elevated in AD. Distinct IL-22-producing CD4+ and CD8+ T-cell populations were significantly increased in AD skin compared with psoriasis. IL-22+CD8+ T-cell frequency correlated with AD disease severity.Conclusion Our data established that T cells could independently express IL-22 even with low expression levels of IL-17. This argues for a functional specialization of T cells such that "T17" and "T22" T-cells may drive different features of epidermal pathology in inflammatory skin diseases, including induction of antimicrobial peptides for "T17" T cells and epidermal hyperplasia for "T22" T-cells. Given the clinical correlation with disease severity, further characterization of "T22" T cells is warranted, and may have future therapeutic implications.
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Circulating IL-22 correlates with AD severity and appears to be a key driver of the inflammatory reaction.
“Circulating IL-22 correlates with the severity of AD and appears as a key driver in the inflammatory reaction116,119.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [116]
The Results (page unavailable) correlate the frequency of IL-22-producing CD8+ T cells in AD lesions—not circulating IL-22—with disease severity. The Discussion (page unavailable) suggests an IL-22 contribution to skin changes, but does not establish it as a key driver of the inflammatory reaction. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIL-22 is an important part of the transcriptomic signature in AD.
“IL-22 is an important part of the transcriptomic signature in AD116,117.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [116]
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Human Langerhans cells induce distinct IL-22-producing CD4 + T cells lacking IL-17 production
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Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling
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Self-citation
- Authors
- Nograles, K. E., Zaba, L. C., Shemer, A., Fuentes-Duculan, J., Cardinale, I., Kikuchi, T., Ramon, M., Bergman, R., Krueger, J. G., & Guttman-Yassky, E.
- Affiliations
- Rockefeller University (US)
- Technion – Israel Institute of Technology (IL)
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 123
- Issue
- 6
- Pages
- 1244-1252.e2
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC2874584
- OpenAlex
- W2164098277
- Cited by
- 627
- References
- 30
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 21 · 2023: 23 · 2022: 28 · 2021: 39 · 2020: 39 · 2019: 28 · 2018: 25 · 2017: 49 · 2016: 49 · 2015: 51 · 2014: 52 · 2013: 34 · 2012: 47
- FWCI
- 65.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 07739, T32GM007739)
- National Center for Research Resources (UL1RR024143)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- atopic dermatitis, IL-22, IL-17, Th17 cells, Th2 cells, Th1 cells, IL-23, psoriasis, CD4+ T cells, CD8+ T cells, disease severity, epidermal hyperplasia, antimicrobial peptides, skin inflammation
- MeSH terms
- Interleukin-22, Adult, Chronic Disease, Dermatitis, Atopic, T-Lymphocytes, Helper-Inducer, Humans, Interleukins, Middle Aged, Psoriasis, T-Lymphocyte Subsets, Interleukin-17, Interleukin-23
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